- Email: [email protected]
Elderly Cirrhotic Patients with Pre-Dementia Mild Cognitive Impairment and Minimal Hepatic Encephalopathy Have a Distinct Cognitive and Brain MR Profile
POSTER PRESENTATIONS Methods: Patients: 218 patients admitted to the hospital for complications of cirrhosis were prospectively studied. Urinary levels of MCP-1 and other proinflammatroy biomarkers: osteopontin (OPN), trefoil-factor3 (TTF3) and liver-fatty-acidbinding protein (LFAB), were measured at admission (RBM Human KidneyToxicity Panel 2, Bio-Rad). Non inflammatory mediators such as cystatin-C (Cys-C) and beta-2-microglobulin (β2M) were also measured as control biomarkers. The relationship between these biomarkers and the 3-month probability of readmission to hospital and mortality were assessed. Results: 67 patients (31%) had at least one episode of readmission during the 3 month period of follow-up and 30 patients died (14%). In the whole series, urinary levels of the proinflammatory biomarkers were significantly higher compared to those of a control group of healthy subjects. Among all proinflamatory biomarkers analysed, only MCP-1 and OPN, were associated with 3-month probability of readmission (0.85 vs 0.48 μg/g creat and 2039 vs 1132 ug/g creat, in patients with and without readmission, respectively; p < 0.05; median (IQR)). Furthermore urinary levels of MCP-1 and OPN were significantly associated with mortality (1.01 vs 0.48 μg/g creat and 2324 vs 1225 μg/g creat, in dead and alive patients at 3 months; p < 0.05, respectively). MCP-1 was the only independent predictive factor of readmission and mortality at 3 months. Conclusions: Urinary levels of MCP-1 are elevated in decompensated cirrhosis and are an independent predictive factor of poor outcome. These results suggest that in cirrhosis there is an inflammatory response that is associated with poor prognosis.
ACLF gps had higher admission MELD/WBC, greater % SIRS/infections, & highest unadjusted in-hospital mortality (Table). While unadjusted in-hospital mortality was higher for ACLF + HE groups vs. no-ACLF/HE gps (all p < 0.001) & in those with higher HE grade + ACLF compared to lower grades with ACLF ( p = 0.01), when adjusted for organ failures, age, WBC, infections & SIRS on regression, only HE grade remained significant (grade 3–4 HE/ACLF vs 1–2 HE/ACLF OR 4.0 p = 0.04). Regional comparison: 533 were in Gp 1, 374 in gp 2, 375 in gp 3 & 281 pts in gp 4. Demographics, MELD score, %SIRS/prior HE, & infections/ACLF were similar between regions. Rifaximin use was lowest (6% gp 4 vs. 50%, 39% & 44% in gps 1–3, p < 0.0001), while admission creatinine (2.3 vs. 1.4, 1.3, 1.5, p = 0.003) & in-hospital mortality were highest (10% gp 4 vs. 6%, 5%, 5% in gps 1–3, p = 0.05) in Gp4. The high gp 4 mortality was significant on regression (adjusted OR gp 4 compared to gp 1:5.6, vs gp 2 OR: 6.3, vs gp 3: 7.1, p < 0.0001).
THU-334 IN-HOSPITAL MORTALITY RELATED TO HEPATIC ENCEPHALOPATHY IS INDEPENDENT OF ACUTE-ON-CHRONIC LIVER FAILURE AND VARIES SIGNIFICANTLY ACROSS NORTH AMERICA: NACSELD EXPERIENCE J.S. Bajaj1, K. Reddy2, P. Tandon3, G. Garcia-Tsao4, F. Wong5, P. Kamath6, S. Biggins7, M. Fallon8, B. Maliakkal9, P. Thuluvath10, R. Subramanian11, H. Vargas12, J. Lai13, L. Thacker1, J. O’leary14 and NACSELD. 1Virginia Commonwealth University, Richmond; 2University of Pennsylvania, Philadephia, United States; 3University of Alberta, Edmonton, Canada; 4 Yale University Medical Center, New Haven, United States; 5University of Toronto, Toronto, Canada; 6Mayo Clinic School of Medicine, Rochester; 7 University of Colorado, Denver; 8University of Texas, Houston; 9 University of Rochester, Rochester; 10Mercy Medical Center, Baltimore; 11 Emory University Medical Center, Atlanta; 12Mayo Clinic, Scottsdale; 13 University of California, San Francisco; 14Baylor University Medical Center, Dallas, United States E-mail: [email protected] Background and Aims: Hepatic encephalopathy (HE) is a part of acute-on-chronic liver failure (ACLF) but its competing impact with ACLF on in-hospital mortality is unclear. Aim: 1. Define the contribution of HE with/without ACLF on in-hospital mortality in NACSELD (North American Consortium for Study of End-stage Liver Disease) 2. Define regional variations in HE outcomes Methods: Cirrhotic inpatients were followed till discharge/inhospital death. Pts were divided by West-Haven criteria (0, 1–2 & 3–4) for HE but ACLF was defined as ≥2 (3–4 HE, ventilation, dialysis or shock). Survival was compared between gps (no HE/no ACLF, 1–2 HE/no ACLF, 1–2 HE/ACLF, 3–4 HE/no ACLF, 3–4 HE/ACLF) & by region using logistic regression. Regions are Gp 1(NE US), Gp 2 (SE US), Gp 3 (SW US) & Gp 4 (Canada). Results: 1522 pts (age 57, MELD 17, 57% prior HE, 38% on rifaximin, 40% infected) were included. During the hospitalization, 517 had HE (372 1–2, 145 grade 3–4) &104 developed ACLF. HE survival): Grade 3–4 vs. Grade 1–2 & no-HE pts had higher MELD (22 vs 18/18, p < 0.0001), ACLF (46% vs 10/4% p < 0.001), diabetes (43% vs 40%/33%, p = 0.03) &in-hospital mortality (27% vs 5%/4%, p < 0.0001). 3–4 HE Inhospital mortality was highest(OR 3.3, p < 0.0001) independent of MELD, WBC &non-HE organ failures. HE/ACLF interaction: Both HE +
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Conclusions: HE is a significant determinant of in-hospital mortality with or without the presence of ACLF. There is considerable regional variation within North America with HE-related in-hospital mortality. THU-335 ELDERLY CIRRHOTIC PATIENTS WITH PRE-DEMENTIA MILD COGNITIVE IMPAIRMENT AND MINIMAL HEPATIC ENCEPHALOPATHY HAVE A DISTINCT COGNITIVE AND BRAIN MR PROFILE V. Ahluwahlia1, J. Wade1, F. Moeller1, J. Steinberg1, M. White1, A. Unser1, A. Fagan1, D. Ganapathy1, R. Sterling1, R.T. Stravitz1, S. Matherly1, V. Luketic1, A. Sanyal1, M. Siddiqui1, P. Puri1, M. Fuchs1, D. Heuman1, J.S.S. Bajaj1. 1Virginia Commonwealth University, Richmond, United States E-mail: [email protected] Background and Aims: As the population with cirrhosis ages, characterization of pre-dementia mild cognitive impairment (MCI) in the context of cirrhosis-associated minimal hepatic encephalopathy (MHE) is essential to ensure adequate therapy & appropriate transplant work-up. Aim: To define cognitive,
Journal of Hepatology 2016 vol. 64 | S213–S424
POSTER PRESENTATIONS psychological & brain MR spectroscopy (MRS) characteristics of elderly cirrhotics with MHE + MCI compared to non-cirrhotic controls. Methods: Outpatient cirrhotics &age-matched non-cirrhotic patients aged 65–85 years without significant co-morbid conditions (CHF/COPD/cancer) or prior/current overt HE or dementia were included. Cognitive tests were MHE-specific (Psychometric hepatic encephalopathy score, PHES), focused on MCI (Hopkins Verbal Learning, HVLT, Similarities test) and tests that could be impaired on both: RBANS (5 subparts) & EncephalApp Stroop. Quality of life was measured with Sickness Impact Profile (SIP, has total/ psychosocial/physical domains). A brief psychologist interview (who was blinded to the cirrhosis status) after testing was the gold standard to diagnose subjects as Gp A normal, Gp B MCI-type and Gp C MHE + MCI. The cognitive performance & not the cirrhosis status was the basis of this division. A subset underwent same-day MRS of posterior gray & parietal white matter. MRS neuronal (N-acetyl aspartate NAA) & astrocytic (glutamate/glutamine, myoinositol, choline) marker creatine ratios were compared. Results: 50 patients (26 cirrhotic, 73 yrs) were included (Table). All cirrhotics were compensated (median MELD 11, 54% HCV). RBANS sub-parts: delayed memory was the worst in MCI (Gp A: 73 ± 20, B: 21 ± 27, C: 34 ± 26, p < 0.0001), while visuo-spatial (Gp A: 89 ± 13, B: 52 ± 30, 34 ± 29, p < 0.0001) & attention were the worst in MHE + MCI (Gp A: 72 ± 25, B: 61 ± 33, C: 40 ± 24, p < 0.005). Language/immediate memory were equally impaired in both affected gps. MHE + MCI pts had the worst total (Gp A: 1.3 ± 1.5, B: 7 ± 7, C: 9 ± 12, p = 0.03) & physical SIP (Gp A: 1 ± 2, B: 5 ± 7, C: 10 ± 12, p = 0.02).
MRS: 26 pts (12 normal, 7 MCI, 7 MHE + MCI) underwent MRS. A significant neuronal impairment (NAA reduction) was seen in MHE + MCI compared to MCI only/normal cognition in parietal white (1.2 ± 0.6 vs 1.8 ± 0.2 vs 1.7 ± 0.2, p = 0.02) & gray matter (1.1 ± 0.1 vs 1.3 ± 0.1 vs 1.3 ± 0.2, p = 0.01) without astrocytic changes. Conclusions: Elderly patients with MHE + MCI have a distinct cognitive profile that is associated with poor QOL. This profile is associated with neuronal impairment on brain MR spectroscopy and could help classify the rapidly growing elderly cirrhosis population. THU-336 COST EFFECTIVENESS OF COVERED TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT VERSUS ENDOSCOPIC TREATMENT FOR SECONDARY PREVENTION OF GASTRO-OESOPHAGEAL VARICEAL BLEEDING J. Harki1, I. Lisanne Holster1, S. Polinder2, A. Moelker3, H.R. van Buuren1, E.J. Kuipers1,4, E.T.T.L. Tjwa1. 1Gastroenterology and Hepatology; 2Public Health; 3Radiology; 4Internal Medicine, Erasmus Mc University Medical Centre Rotterdam, Rotterdam, Netherlands E-mail: [email protected]
Background and Aims: Endoscopic variceal ligation (EVL) is the accepted first line therapy for the secondary prevention of gastroesophageal variceal bleeding (GEVB). Recent data suggest that transjugular intrahepatic portosystemic shunt (TIPS) is more effective and may become the preferred treatment. However, the comparative costs of these treatment strategies have not been well defined. We aimed to compare the total health care costs of TIPS placement versus EVL + β-blocker for the secondary prevention of GEVB in the first year following the index bleeding. Methods: Health care consumption data were based on observed data in 52 patients (25 TIPS/27 endoscopy) surviving an acute first or second variceal bleeding due to liver cirrhosis-related portal hypertension in a multicenter, randomized controlled trial. The primary endpoint of this study was defined as mean total health care costs per patient for the two treatment strategies.
Results: Twenty-five patients (age 56 (IQR 49-60) years; 13 males) were randomized to TIPS placement versus 27 patients (age 54 (IQR 49-63) years; 16 males) to treatment with EVL. The mean total costs per patient were significantly higher in the TIPS group compared to the EVL group (€27.746 vs. €16.818, p = 0.006). The highest cost category for the TIPS group were costs of the intervention (mean cost per patient €8.673 for TIPS placement vs. € 328 for EVL, p = < 0.001) and re-intervention (mean cost per patient per TIPS revision were €1.388). Intramural care, consisting of hospital admissions, ICU care, and treatment in daycare setting were the highest cost categories for the EVL treatment arm (mean total cost per patient €5.612 and €1.440 for patients treated with EVL for admission on ward in an academic hospital and community hospital, respectively, see Table 1). Conclusions: Treatment with TIPS after an acute episode of GEVB has significantly higher treatment costs in the first year after treatment compared to patients treated with EVL. This cost consideration should play a role in selection of the most optimal treatment. From an economic point of view, treatment with endoscopic variceal band ligation is recommended for the
Journal of Hepatology 2016 vol. 64 | S213–S424
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ACLF gps had higher admission MELD/WBC, greater % SIRS/infections, & highest unadjusted in-hospital mortality (Table). While unadjusted in-hospital mortality was higher for ACLF + HE groups vs. no-ACLF/HE gps (all p < 0.001) & in those with higher HE grade + ACLF compared to lower grades with ACLF ( p = 0.01), when adjusted for organ failures, age, WBC, infections & SIRS on regression, only HE grade remained significant (grade 3–4 HE/ACLF vs 1–2 HE/ACLF OR 4.0 p = 0.04). Regional comparison: 533 were in Gp 1, 374 in gp 2, 375 in gp 3 & 281 pts in gp 4. Demographics, MELD score, %SIRS/prior HE, & infections/ACLF were similar between regions. Rifaximin use was lowest (6% gp 4 vs. 50%, 39% & 44% in gps 1–3, p < 0.0001), while admission creatinine (2.3 vs. 1.4, 1.3, 1.5, p = 0.003) & in-hospital mortality were highest (10% gp 4 vs. 6%, 5%, 5% in gps 1–3, p = 0.05) in Gp4. The high gp 4 mortality was significant on regression (adjusted OR gp 4 compared to gp 1:5.6, vs gp 2 OR: 6.3, vs gp 3: 7.1, p < 0.0001).
THU-334 IN-HOSPITAL MORTALITY RELATED TO HEPATIC ENCEPHALOPATHY IS INDEPENDENT OF ACUTE-ON-CHRONIC LIVER FAILURE AND VARIES SIGNIFICANTLY ACROSS NORTH AMERICA: NACSELD EXPERIENCE J.S. Bajaj1, K. Reddy2, P. Tandon3, G. Garcia-Tsao4, F. Wong5, P. Kamath6, S. Biggins7, M. Fallon8, B. Maliakkal9, P. Thuluvath10, R. Subramanian11, H. Vargas12, J. Lai13, L. Thacker1, J. O’leary14 and NACSELD. 1Virginia Commonwealth University, Richmond; 2University of Pennsylvania, Philadephia, United States; 3University of Alberta, Edmonton, Canada; 4 Yale University Medical Center, New Haven, United States; 5University of Toronto, Toronto, Canada; 6Mayo Clinic School of Medicine, Rochester; 7 University of Colorado, Denver; 8University of Texas, Houston; 9 University of Rochester, Rochester; 10Mercy Medical Center, Baltimore; 11 Emory University Medical Center, Atlanta; 12Mayo Clinic, Scottsdale; 13 University of California, San Francisco; 14Baylor University Medical Center, Dallas, United States E-mail: [email protected] Background and Aims: Hepatic encephalopathy (HE) is a part of acute-on-chronic liver failure (ACLF) but its competing impact with ACLF on in-hospital mortality is unclear. Aim: 1. Define the contribution of HE with/without ACLF on in-hospital mortality in NACSELD (North American Consortium for Study of End-stage Liver Disease) 2. Define regional variations in HE outcomes Methods: Cirrhotic inpatients were followed till discharge/inhospital death. Pts were divided by West-Haven criteria (0, 1–2 & 3–4) for HE but ACLF was defined as ≥2 (3–4 HE, ventilation, dialysis or shock). Survival was compared between gps (no HE/no ACLF, 1–2 HE/no ACLF, 1–2 HE/ACLF, 3–4 HE/no ACLF, 3–4 HE/ACLF) & by region using logistic regression. Regions are Gp 1(NE US), Gp 2 (SE US), Gp 3 (SW US) & Gp 4 (Canada). Results: 1522 pts (age 57, MELD 17, 57% prior HE, 38% on rifaximin, 40% infected) were included. During the hospitalization, 517 had HE (372 1–2, 145 grade 3–4) &104 developed ACLF. HE survival): Grade 3–4 vs. Grade 1–2 & no-HE pts had higher MELD (22 vs 18/18, p < 0.0001), ACLF (46% vs 10/4% p < 0.001), diabetes (43% vs 40%/33%, p = 0.03) &in-hospital mortality (27% vs 5%/4%, p < 0.0001). 3–4 HE Inhospital mortality was highest(OR 3.3, p < 0.0001) independent of MELD, WBC &non-HE organ failures. HE/ACLF interaction: Both HE +
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Conclusions: HE is a significant determinant of in-hospital mortality with or without the presence of ACLF. There is considerable regional variation within North America with HE-related in-hospital mortality. THU-335 ELDERLY CIRRHOTIC PATIENTS WITH PRE-DEMENTIA MILD COGNITIVE IMPAIRMENT AND MINIMAL HEPATIC ENCEPHALOPATHY HAVE A DISTINCT COGNITIVE AND BRAIN MR PROFILE V. Ahluwahlia1, J. Wade1, F. Moeller1, J. Steinberg1, M. White1, A. Unser1, A. Fagan1, D. Ganapathy1, R. Sterling1, R.T. Stravitz1, S. Matherly1, V. Luketic1, A. Sanyal1, M. Siddiqui1, P. Puri1, M. Fuchs1, D. Heuman1, J.S.S. Bajaj1. 1Virginia Commonwealth University, Richmond, United States E-mail: [email protected] Background and Aims: As the population with cirrhosis ages, characterization of pre-dementia mild cognitive impairment (MCI) in the context of cirrhosis-associated minimal hepatic encephalopathy (MHE) is essential to ensure adequate therapy & appropriate transplant work-up. Aim: To define cognitive,
Journal of Hepatology 2016 vol. 64 | S213–S424
POSTER PRESENTATIONS psychological & brain MR spectroscopy (MRS) characteristics of elderly cirrhotics with MHE + MCI compared to non-cirrhotic controls. Methods: Outpatient cirrhotics &age-matched non-cirrhotic patients aged 65–85 years without significant co-morbid conditions (CHF/COPD/cancer) or prior/current overt HE or dementia were included. Cognitive tests were MHE-specific (Psychometric hepatic encephalopathy score, PHES), focused on MCI (Hopkins Verbal Learning, HVLT, Similarities test) and tests that could be impaired on both: RBANS (5 subparts) & EncephalApp Stroop. Quality of life was measured with Sickness Impact Profile (SIP, has total/ psychosocial/physical domains). A brief psychologist interview (who was blinded to the cirrhosis status) after testing was the gold standard to diagnose subjects as Gp A normal, Gp B MCI-type and Gp C MHE + MCI. The cognitive performance & not the cirrhosis status was the basis of this division. A subset underwent same-day MRS of posterior gray & parietal white matter. MRS neuronal (N-acetyl aspartate NAA) & astrocytic (glutamate/glutamine, myoinositol, choline) marker creatine ratios were compared. Results: 50 patients (26 cirrhotic, 73 yrs) were included (Table). All cirrhotics were compensated (median MELD 11, 54% HCV). RBANS sub-parts: delayed memory was the worst in MCI (Gp A: 73 ± 20, B: 21 ± 27, C: 34 ± 26, p < 0.0001), while visuo-spatial (Gp A: 89 ± 13, B: 52 ± 30, 34 ± 29, p < 0.0001) & attention were the worst in MHE + MCI (Gp A: 72 ± 25, B: 61 ± 33, C: 40 ± 24, p < 0.005). Language/immediate memory were equally impaired in both affected gps. MHE + MCI pts had the worst total (Gp A: 1.3 ± 1.5, B: 7 ± 7, C: 9 ± 12, p = 0.03) & physical SIP (Gp A: 1 ± 2, B: 5 ± 7, C: 10 ± 12, p = 0.02).
MRS: 26 pts (12 normal, 7 MCI, 7 MHE + MCI) underwent MRS. A significant neuronal impairment (NAA reduction) was seen in MHE + MCI compared to MCI only/normal cognition in parietal white (1.2 ± 0.6 vs 1.8 ± 0.2 vs 1.7 ± 0.2, p = 0.02) & gray matter (1.1 ± 0.1 vs 1.3 ± 0.1 vs 1.3 ± 0.2, p = 0.01) without astrocytic changes. Conclusions: Elderly patients with MHE + MCI have a distinct cognitive profile that is associated with poor QOL. This profile is associated with neuronal impairment on brain MR spectroscopy and could help classify the rapidly growing elderly cirrhosis population. THU-336 COST EFFECTIVENESS OF COVERED TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT VERSUS ENDOSCOPIC TREATMENT FOR SECONDARY PREVENTION OF GASTRO-OESOPHAGEAL VARICEAL BLEEDING J. Harki1, I. Lisanne Holster1, S. Polinder2, A. Moelker3, H.R. van Buuren1, E.J. Kuipers1,4, E.T.T.L. Tjwa1. 1Gastroenterology and Hepatology; 2Public Health; 3Radiology; 4Internal Medicine, Erasmus Mc University Medical Centre Rotterdam, Rotterdam, Netherlands E-mail: [email protected]
Background and Aims: Endoscopic variceal ligation (EVL) is the accepted first line therapy for the secondary prevention of gastroesophageal variceal bleeding (GEVB). Recent data suggest that transjugular intrahepatic portosystemic shunt (TIPS) is more effective and may become the preferred treatment. However, the comparative costs of these treatment strategies have not been well defined. We aimed to compare the total health care costs of TIPS placement versus EVL + β-blocker for the secondary prevention of GEVB in the first year following the index bleeding. Methods: Health care consumption data were based on observed data in 52 patients (25 TIPS/27 endoscopy) surviving an acute first or second variceal bleeding due to liver cirrhosis-related portal hypertension in a multicenter, randomized controlled trial. The primary endpoint of this study was defined as mean total health care costs per patient for the two treatment strategies.
Results: Twenty-five patients (age 56 (IQR 49-60) years; 13 males) were randomized to TIPS placement versus 27 patients (age 54 (IQR 49-63) years; 16 males) to treatment with EVL. The mean total costs per patient were significantly higher in the TIPS group compared to the EVL group (€27.746 vs. €16.818, p = 0.006). The highest cost category for the TIPS group were costs of the intervention (mean cost per patient €8.673 for TIPS placement vs. € 328 for EVL, p = < 0.001) and re-intervention (mean cost per patient per TIPS revision were €1.388). Intramural care, consisting of hospital admissions, ICU care, and treatment in daycare setting were the highest cost categories for the EVL treatment arm (mean total cost per patient €5.612 and €1.440 for patients treated with EVL for admission on ward in an academic hospital and community hospital, respectively, see Table 1). Conclusions: Treatment with TIPS after an acute episode of GEVB has significantly higher treatment costs in the first year after treatment compared to patients treated with EVL. This cost consideration should play a role in selection of the most optimal treatment. From an economic point of view, treatment with endoscopic variceal band ligation is recommended for the
Journal of Hepatology 2016 vol. 64 | S213–S424
S265