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Acute on Chronic Liver Failure: Practical Management Outside the Tertiary Centre

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King’s College Hospital NHS Foundation Trust NHS Acute on Chronic Liver Failure: Practical management outside the tertiary centre. William Bernal Professor of Liver Critical Care Liver Intensive Therapy Unit Institute of Liver Studies Kings College Hospital United Kingdom ACLF & Practical Management ACLF & Practical Management Admissions: Liver Critical Care Kings College Hospital 2016/17 n=1569 Hepatobiliary Surgery Acute liver failure Chronic liver disease Transplants Previous Transplants Non Liver Patients ACLF & Practical Management Intensive Care National Audit and Research Centre (ICNARC) Extrapolated numbers of cirrhosis ICU admissions and ICU deaths per 100,000 population (England, Wales & NI) 10 9 8 7 6 5 4 3 2 Numberper100,000 population 1 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Year Admissions Deaths © ICNARC 2015 McPhail et al Manuscript Submitted 2017 ACLF & Practical Management Mortality from chronic liver disease, all ages, England, 1995-2014 18 7,000 16 6,000 (persons) Number of deaths 14 5,000 12 10 4,000 8 3,000 6 2,000 4 Directly standardised mortality rate 1,000 2 Number of deaths (persons) 0 0 Directly standardised mortality per rate 100,000mortality Directly standardised Source: NHS Atlas of Variation in healthcare for people with liver disease 2017 (In press) Acute on Chronic Liver Failure (ACLF): Practical management outside the tertiary centre. Overview: • ACLF in the natural history of Chronic Liver Disease. – Definitions – Controversies • ACLF: practical Issues in clinical care. – Getting access to ICU: avoiding futility. – Ward Interventions: preventing ACLF. • ACLF: how can your Liver Unit help? – Transfer – Transplantation. Natural History Chronic Liver Disease. Compensated Cirrhosis No ascites or overt HE Recompensation ~ 5-10% patients / year of hepatic function Decompensated Cirrhosis Ascites, HE, Variceal bleeding Natural History Chronic Liver Disease. D’Amico et al J Hepatology 2006;44:217-231 Natural History Chronic Liver Disease Complication 1Year Mortality Variceal Bleeding 20% Ascites 29% Ascites and Variceal Bleeding 49% Hepatic Encephalopathy 64% Jepsen et al Hepatology 2010;51:1675-82. n=466 Natural History Chronic Liver Disease. Compensated Cirrhosis No ascites or overt HE Recompensation ~ 5-10% patients / year of hepatic function Decompensated Cirrhosis Ascites, HE, Variceal bleeding Resolution ~ 30% hospitalised patients of organ failures Acute on Chronic Liver Failure (ACLF) Hepatic and Extra-hepatic organ failure ? Up to 50% hospitalised patients Death ACLF & Practical Management Acute on Chronic Liver Failure (ACLF) “Acute on chronic liver failure is a syndrome in patients with chronic liver disease with or without cirrhosis which is characterized by acute hepatic decompensation resulting in liver failure (jaundice and prolongation of the INR) and one or more extra-hepatic organ failures that is associated with increased mortality within a period of 28 days from onset..’ World Congress of Gastroenterology Gastroenterology 2014 ;147(1);4-10 ACLF & Practical Management • Who are we discussing? – Cirrhotic – Precipitating event • Bleeding / Sepsis / Drug effect – Hepatic failure • Jaundiced, coagulopathic – Extra-hepatic organ failure • Encephalopathy • Hypotension • Renal dysfunction ACLF & Practical Management CANONIC: Chronic liver failure Acute On-chronic liver failure In Cirrhosis 29 Liver Units, 8 European Countries 1343 Hospitalised patients with cirrhosis Develop a definition and scoring system for ACLF. Moreau et al Gastroenterology 2013 144: 1426-13 ACLF & Practical Management http://www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ACLF & Practical Management CLIF Organ Failures Organ System Criteria Hepatic Bilirubin ≥ 200 mMol / L Cerebral Encephalopathy ≥ Grade 3 Renal Creatinine ≥ 180 mMol/L and / or use of renal replacement therapy Coagulation INR >2.5 and / or platelet count ≤ 20 x 109/L Circulation Use of vasopressor agents and / or terlipressin Respiratory Ratio of partial pressure of oxygen/ inspired oxygen ≤ 200 or Ratio of Pulse oximetry saturation / inspired oxygen ≤214 Moreau et al Gastroenterology. 2013 Jun;144(7):1426-37.e9. ACLF & Practical Management ACLF Grades ACLF-1 Renal or cerebral failure alone or renal dysfunction with other organ failure. ACLF-2 Two Organ Failures. ACLF-3 Three or More Organ Failures. Moreau et al Gastroenterology 2013 144: 1426-13 ACLF & Practical Management ACLF Grade and Mortality. 90 80 70 60 50 40 Mortality (%) Mortality 30 20 10 0 No ACLF ACLF 1 ACLF 2 ACLF 3 28-Day 90-Day Moreau et al Gastroenterology 2013 144: 1426-13 ACLF & Practical Management Reported Triggers to ACLF; Europe and China. 50 45 40 35 30 25 20 15 % of ACLF Cases ACLF % of 10 5 0 Reactivation Bacterial GI Bleed Active Other Not More than 1 HBV Infection Alcohol Identifiable CANONIC Shi et al CANONIC n=303 Gastro. 2013 144: 1426-13 Shi et al n=405 Hepatology 2015 62:232-42 ACLF & Practical Management ACLF: Systemic Inflammation & Severity of Illness Inflammatory markers at enrolment in CANONIC Study. n=1343 Leucocyte Count C-Reactive Protein 14 70 12 60 /l 9 10 50 8 40 6 30 4 20 CRP mg/l CRP 2 WBC x 10 WBC x 10 0 0 No ACLF ACLF 1 ACLF 2 ACLF 3 No ACLF ACLF 1 ACLF 2 ACLF 3 Moreau et al Gastroenterology 2013 144: 1426-13 ACLF & Practical Management Plasma Cytokine Concentrations according to Precipitating Event for ACLF Claria et al Hepatology 2016 64(4) 1249-1264 n=237 Measurements at study enrolment TNF-α Interleukin-6 Interleukin-8 40 90 250 35 80 200 30 70 60 25 150 50 /ml 20 40 100 pg 15 30 10 20 50 5 10 0 0 0 P<0.03 P<0.0001 P<0.0001 ACLF & Practical Management • ACLF: Definition – Precipitating event, hepatic and extra-hepatic OF. – High short term mortality. – Key to research and defining practice. • ACLF: Controversies – Heterogeneous precipitants? – Unified pathophysiology? – No identifiable precipitants? – Scores to instruct care? ACLF & Practical Management. Critical Care: Inevitable Destination? ACLF & Practical Management. Critical Care: Admission Impossible? ACLF & Practical Management Escalation of care? NCEPOD 2013 Alcohol Related Liver Disease: Measuring the Units ‘Both Advisors and clinicians identified patients in whom escalation of care was not received despite it being indicated..’ ‘..Escalation of care should be actively pursued for patients with Alcohol-related Liver disease who deteriorate acutely and whose background functional status is good. There should be close liaison between the medical and critical care teams when making escalation decisions..’ www.ncepod.org.uk ACLF & Practical Management Escalation of care? Barriers to Critical Care: Aetiology. ACLF & Practical Management Escalation of care? Barriers to Critical Care: Outcome Study Year n ICU Mortality Cholongitas et al 2006 312 65% Alim Pharm Ther 2006;23:883-893 Fang et al 2008 111 81% Neph Dial Trans 2008;23(6):1961-9 Junea et al 2009 104 42% J Crit Care 2009;24(3):387-93 Thompson et al 2010 137 47% Aliment Pharmacol Ther 2010; 32: 233–243 Das et al 2010 138 41% Crit Care Med 2010 38:2108-2116 Tu et al 2011 202 60% Shock 2011 36:445-450 Olemz et al 2012 201 42% Ann Hepatol 2012 1;513-518 Levesque et al 2012 377 43% J Hep 2012 56:95-102 Frolich et al 2014 170 60% J Crit Care 2014 29;6: 1131 McPhail et al 2015 971 49% Clinical Gastro Hep 13(7) 1353-60 ACLF & Practical Management Escalation of care? Barriers to Critical Care: Outcome Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis. Weil et al Annals of Intensive Care 2017 7:33 13 Studies 2532 patients 1995-2012 Mortality ICU 43% Hospital 54% 6-Month 75% ACLF & Practical Management Escalation of care? Barriers to Care: Resource Use Liver ITU Kings College Hospital ACLF admissions 2003-2007 • 534 Patients 226 (42%) ICU mortality • 80% 2 or more organ failures Average cost per Patient £28,409 Average cost per Survivor £23,206 Average cost per Non-survivor £37,329 Effective cost per Survivor £51,198 Shawcross et al J Hepatol 2012; 56(5):1054-62 ACLF & Practical Management Escalation of care? High resistance to ICU admission – Constrained resources. – ‘Self inflicted’ aetiologies. – High resource use and cost. – ICU / Post-ITU Mortality high. – Preconception of futility. ACLF & Practical Management Escalation of care? Futile Critical Care? Mortality of cirrhotic patients admitted to LITU, Kings College Hospital 2000-2010 n=971 p<0.001 Log-rank for comparison of Eras McPhail et al Clin Gastro Hep 2015;13:1353–1360 ACLF & Practical Management Escalation of care? Avoiding Futility: Admission and level of support? – Standard ICU considerations • Age • Co morbidity • Functional / nutritional state • Severity of acute illness – Liver-specific considerations • Liver disease severity • Indication for admission ACLF & Practical Management Escalation of care? Avoiding Futility: Age and Etiology? Weil et al Annals of Intensive Care 2017 7:33 ACLF & Practical Management Escalation of care? Avoiding Futility: prognostic assessment ? • Scoring Tools – Child-Pugh Classification (CPC) – Model for End-stage Liver Disease (MELD) – Sequential Organ Failure Assessment (SOFA) – Chronic Liver Failure Score (CLIF) ACLF & Practical Management Escalation of care? Avoiding Futility: prognostic assessment ? Hospital Survival in ITU Admissions with Cirrhosis KCH 2000-2010 n=933 Score AUROC (95% CI) CLIF 0.813 (0.787-0.837) SOFA 0.799 (0.772-0.823) APA II 0.768 (0.724-0.806) SAPS II 0.781 (0.753-0.806) MELD 0.786 (0.758-0.811) McPhail et al Clin Gastro Hep 2015;13:1353–1360 ACLF & Practical Management Escalation of care? Avoiding Futility: prognostic assessment ? Time of Assessment AUROC Score Admission 72 Hrs MELD 0.79 0.78 SOFA 0.80 0.84 CLIF-SOFA 0.81 0.85 McPhail et al Clin Gastro Hep 2015;13:1353–1360 ACLF & Practical Management Withdrawal of Care? Avoiding Futility: prognostic assessment. ACLF Scores to withdraw care? Hernaez et al Gut 2017; 61:541-553 ACLF & Practical Management Avoiding Futility: Indications for Admission Variceal Bleeding Encephalopathy Renal failure ACLF & Practical Management.
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