Slide 1: Appropriate Patient Selection as a Key to Increase the Benefit/Risk Ratio for ELAD
APPROPRIATE PATIENT SELECTION AS A KEY TO INCREASE THE BENEFIT/RISK RATIO FOR ELAD Ram Subramanian M.D. Hepatology and Critical Care Emory University School of Medicine Atlanta, USA
Slide 2: Outline
OUTLINE Review the prognostic utility of the MELD score in liver disease and failure Examine survival analysis results in the VTI-208 ELAD study, and discuss implications of findings regarding high MELD pts Describe the complex multi-organ system derangements in high MELD patients that pose challeng
Slide 3: Estimated 3-month survival as a function of the MELD score in patients with cirrhosis
Estimated 3-month survival as a function of the MELD score in patients with cirrhosis H i i H E 20 MELD score Wiesner et al. Gastro 2003 MELD : f (INR, Bili, Cr)
Slide 4: Applications of MELD Related Prognosis
APPLICATIONS OF MELD RELATED PROGNOSIS ¢ Cirrhosis: Higher MELD patients associated with: — Higher risk of variceal bleeding (Amitrano et al. J. of Hep 2005) Higher risk of infections (Alessandria et al. Hepatology 2005) Higher risk of AKI (Moreau et al. Gastro 2013 ) Higher ICU mortality ( Karvella
Slide 5: VTI-208 survival analysis by MELD score
n= 203, n= 120, HR=1.027, log rank 0.9 HR = 0.58, log rank 0.077
Slide 6: Schematic for Liver Support in the High MELD patient
Schematic for Liver Support in the High MELD patient MARS/ ELAD CNS ALF, ACLF, AAH / / 19s — ose cv Aggressive ~ Renal + * management Impaired hepatic regeneration ELAD
Slide 7: Management Challenges in High MELD Patients Related to ELAD
Management Challenges in High MELD Patients Related to ELAD
Slide 8: Multi-Organ Dysfunction in Liver Failure
Multi-Organ Dysfunction in Liver Failure Hepatic Encephalopathy Acute Lung Injury Distributive Shock Portal HTN: - Variceal bleeding - Ascites/ SBP Acute Kidney Injury - Coagulopathy - Metabolic Acidosis - Immunocompromised state: infectious complications
Slide 9: Hepatic Encephalopathy (HE)
Hepatic Encephalopathy (HE) Can progress to severe HE refractory to maximal medical therapy and requiring intubation for airway protection Candidate toxins: ammonia, endogenous benzodiazepines, cytokines related to septic encephalopathy Role for MARS: Multiple studies, including RCT (Hassenein et al
Slide 10: Hemodynamic Derangements in Cirrhosis
Hemodynamic Derangements in Cirrhosis CIRRHOSIS. | Portal (sinusoidal) hypertension | SPLANCHNIC / SYSTEMIC VASODILATATION J Decreased effective arterial blood volume J Activation of neurohumoral systems (RAAS, SNS, ADH) Sodium and water retention Renal vasoconstriction I Decreased renal blood flow
Slide 11: Hemodynamic Challenges (1)
HEMODYNAMIC CHALLENGES (1) Baseline abnormal cirrhotic hemodynamics characterized by low MAP mediated by splanchnic and peripheral vasodilation ( How should hypotension/ shock be defined ?) Assessment of fluid/ intravascular status challenging in the critically ill cirrhotic — Static indices of prel
Slide 12: Hemodynamic Challenges (2)
HEMODYNAMIC CHALLENGES (2) Evidence of abnormal myocardial function (cirrhotic cardiomyopathy), characterized by systolic & diastolic dysfunction, and impaired b-adrenergic receptor function In the setting of tense ascites, cardiac preload can be compromised by IVC compression due to abdominal compa
Slide 13: Pulmonary Challenges
PULMONARY CHALLENGES Immunocompromised state risk factor for both intra-thoracic and extra- thoracic infection triggered ARDS ( Bajaj et al. Hepatology 2012) . Increased mortality of ARDS in setting of cirrhosis (Monchi et al. 1998) Evidence supportive of decreased alveolar macrophage and T cell act
Slide 14: Renal Challenges
RENAL CHALLENGES Tenuous baseline cirrhotic hemodynamics predisposes to development of AKI in the setting of minimal cardiovascular insults (implications for extracorporeal therapy in high MELD patients?) Recent multi-center European study identified AKI as most common extrahepatic injury in ACLF an
Slide 15: Hematologic Challenges (1)
HEMATOLOGIC CHALLENGES (1) Given the depletion of both procoagulant and anticoagulant proteins, the net state of coagulopathy is unpredictable Conventional measures of coagulation ( e.g. INR, PT) not applicable; role for TEG ? The presence of infection and sepsis can trigger: — a prothrombotic casca
Slide 16: Hematologic Issues Related to Liver Support
Hematologic Issues Related to Liver Support Heparin use may influence measures of coagulation in subject, thereby affecting potential study end points related to liver support Titration of heparin challenging, since measures of anticoagulation (e.g. PTT, anti Factor Xa) may be inaccurate due to anti
Slide 17: Infectious Disease Issues
INFECTIOUS DISEASE ISSUES * The patient with decompensated liver disease is an immunocompromised host, and at risk for bacterial, fungal and viral infections Higher MELD patients associated with increased risk of infections (Alessandria et al. Hepatology 2005) Nosocomial infections independent risk
Slide 18: Acute-on-Chronic Liver Failure categories
Acute-on-Chronic Hepatitis Chronic Liver Failure (AOCH) (End Stage Liver Disease) Acute Liver Failure Surgery Induced Live = Failure / SILF aiebelsate iepEEEBOGEO Chronic Alcoholic (Asia) Liver Disease Fulminant Hepatic nee) Hepatitis C FHF =P Alcohol Induced Liver Decompensation / AILD
Slide 19: Summary
SUMMARY The application of extracorporeal liver support in the high MELD patient is challenging, and therefore, appropriate patient selection with respect to hepatic disease severity is crucial. Early and aggressive intensive care support of multi-organ dysfunction is crucial in improving survival.