No ACLF - Chirurgie
Transcription
No ACLF - Chirurgie
Ateliers de Printemps de l'ACHBT 2014 MARSEILLE Vendredi 16 mai 2014 Physiopathologie et histoire naturelle de la cirrhose Richard Moreau,1,2,3 1UMR S_1149, Centre de Recherche sur l’Inflammation (CRI), Inserm et Université Paris-Diderot, Paris 7, 2DHU UNITY, Service d’Hépatologie, Hôpital Beaujon, APHP, Clichy 3Laboratoire d’Excellence (Labex) INFLAMEX, PRES Sorbonne Paris Cité, France [email protected] Natural History of Chronic Liver Disease Development of cirrhosis Chronic liver disease Inflammation Necrosis Fibrosis Hepatocellular carcinoma Compensated cirrhosis Median suvival 9 yr ACLF High risk of death Decompensated Cirrhosis Complications Ascites GI bleeding Median survival 1.6 yr No ACLF No risk of death Persistent insult ACLF, acute-on-chronic liver failure Sommaire • Physiopathologie de la décompensation • ACLF : ‒ Définition ‒ Physiopathologie Augmentation de la résistance vasculaire intrahépatique dans la cirrhose Circulation collatérale portosystémique Distorsion de l’angioarchitecture hépatique Veine porte Diminution de la production locale de NO (monoxyde d’azote) Splénomegalie AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION Dans la cirrhose, une augmentation du débit sanguin dans le territoire de la veine porte maintient l’hypertension portale Distortion de l’angioarchitechure hépatique Veine porte Débit sanguin augmenté Vasodilatation splanchnique (monoxyde d’azote : NO) Pateron et al. Gastroenterology 2000;119:196. Tazi et al. Gastroenterology 2002;122:1869. AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION Dans la cirrhose, la translocation bactérienne intestinale stimule la production artérielle de NO Translocation bactérienne NO Tazi et al. Gastroenterology 2005;129:303. LPS/ cytokines CIRRHOSIS Intrahepatic vascular resistance Systemic arteriolar resistance (dilation) Sinusoidal pressure Effective arterial blood volume (HVPG≥10-12 mm Hg) ASCITES Sodium and water retention Activation of neurohumoral systems (sympathetic, RAAS) HRS Pathophysiology Splanchnic /systemic vasodilation Decreased effective arterial blood volume Decreased cardiac output (reduced venous return) Increased endogenous vasoconstrictor systems Arteriolar vasoconstriction Nonrenal, nonsplanchnic territories Moreau and Lebrec. Hepatology 2006;43:385-94. Renal circulation Decreased GFR RCTs of Terlipressin Plus Albumin in Patients with Type 1 HRS 40 Proportion of patients with HRS reversal % P<0.05 20 0 Albumin 153 patients. Sanyal et al. Gastroenterology 2008;134:1360-8. Martin-Llahi et al. Gastroenterology 2008;134:1352-9. Terlipressin + albumin Sommaire • Physiopathologie de la décompensation • ACLF : ‒ Définition ‒ Physiopathologie Patients of the CANONIC Study • 2149 consecutive patients prospectively evaluated in 29 European hospitals in 12 countries • From February to September, 2011 • Inclusion criteria: ‒ Hospitalized patients with cirrhosis and an acute decompensation of cirrhosis (ascites, GI hemorrhage, encephalopathy, bacterial infection). Moreau et al. Gastroenterology 2013;144:1426-37. Modified Sequential Organ Failure Assessment (SOFA) Score For Patients with Cirrhosis (CLIF-SOFA Score) Organ/system 0 1 2 3 4 <1.2 ≥1.2-<1.9 ≥2-< 5.9 ≥6-<12 ≥12 Kidney: Creatinine, mg/dL <1.2 ≥1.2-<1.9 ≥2-<3.5 ≥3.5-<5 ≥5 Liver: Bilirubin, mg/dL Cerebral (HE grade) No HE 1 2 3 4 Coagulation: INR <1.1 1.1-1.25 1.26-1.5 1.51-2.5 >2.5 or platelets ≤20 x 103 /µL Circulation: MAP (mm Hg) ≥70 <70 Dopamine >5-≤15 ≤5 or or E ≤0.1 dobutamine* or NE ≤0.1 or terlipressin* Lungs: PaO2/FiO2 or SpO2/FiO2 >400 >512 ≤400 ≤300 >357-≤512 >214- ≤357 ≤200 >89- ≤214 >15 >0.1 >0.1 ≤100 ≤89 *any dose. E: epinephrine; NE: norepinephrine; doses for catecholamines are µg/kg.min . Moreau et al. Gastroenterology 2013;144:1426-37. Acute Organ Failures at Admission of Patients with Cirrhosis and Acute Decompensation Patients (N=1,343) 901 Prevalence (%) 67.1 Liver 442 207 32.9 15.4 Kidney (Screat ≥2 mg/dL) 169 12.6 Coagulation 105 7.8 Cerebral 99 7.4 Cardiovascular 64 4.8 Lungs 32 2.4 No organ failure 1 organ failure or more* *Modified SOFA score. Moreau et al. Gastroenterology 2013;144:1426-37. Definition of ACLF and Grades ACLF Grade Definition 28-day Mortality (%) No ACLF • No organ failure (OF) • Single OF (liver, coagulation, circulation, lungs) + Screat <1.5 mg/dL + no HE • Single cerebral failure + Screat <1.5 4.7 • Single kidney failure • Single OF (liver, coagulation, circulation, lungs) + Screat 1.5‒≤1.9 mg/dL and/or grade 1-2 HE • Single cerebral failure + Screat 1.5‒≤1.9 mg/dL 22.1 ACLF-1 ACLF-2 2 OF 32.0 ACLF-3 ≥ 3 OF 78.6 Moreau et al. Gastroenterology 2013;144:1426-37. Moreau et al. Gastroenterology 2013;144:1426-37. Potential Precipitating Events of ACLF at Enrollment in the CANONIC Study No ACLF (N=1040) 226 (21.8) ACLF (N=303) 98 (32.6) P value Active alcoholism within the past 3 months Gastrointestinal hemorrhage 147 (14.9) 69 (24.5) <0.001 180 (17.3) 40 (13.2) 0.09 Other precipitating event 34 (3.5) 25 (8.6) <0.001 584 (58.9) 126 (43.6) <0.001 Bacterial infection No precipitating event Values are n (%). Moreau et al. Gastroenterology 2013;144:1426-37. <0.001 Sommaire • Physiopathologie de la décompensation • ACLF : ‒ Définition ‒ Physiopathologie ACLF is Associated with Systemic Inflammation Leukocyte count* 14 C-reactive Protein* 70 ** 12 ** 60 ** 50 10 8 mg/L x10^9 cells ** * 6 30 4 20 2 10 0 0 NO ACLF ACLF-1 ACLF-2 ACLF-3 ** 40 NO ACLF * p<0.05 with respect to No ACLF ** p<0.001 with respect to No ACLF Moreau et al. Gastroenterology 2013;144:1426-37. ACLF-1 ACLF-2 ACLF-3 Conclusions • La physiopathologie de la décompensation de la cirrhose implique l’hypertension portale et la vasodilatation splanchnique. • L’ACLF est un syndrome distinct de la décompensation. • L’ACLF se développe dans un contexte d’inflammation systémique. Celle-ci peut être en relation avec une infection bactérienne ou la prise d’alcool. Cependant, dans 50 % des cas la cause de l’inflammation reste inexpliquée. AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION Une augmentation du débit sanguin dans le territoire de la veine porte maintient l’hypertension portale Distortion de l’angioarchitechure hépatique Veine porte Débit sanguin augmenté Veines mésenteriques Vasodilatation splanchnique T r T Tension = Pressure x radius (Laplace law) r AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION La vasodilatation splanchnique est impliquée dans le mécanisme des complications de la cirrhose Hémorragies Ascite SHR* *SHR : syndrome hépato-rénal. Vasodilatation splanchnique (NO) AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION Dans la cirrhose, la translocation bactérienne intestinale stimule la production artérielle de NO Translocation bactérienne NO Tazi et al. Gastroenterology 2005;129:303. LPS/ cytokines Strategy Used in the CANONIC Study Prespecified criteria for the diagnosis of ACLF: • Acute decompensation • Organ failure(s) • High in-hospital mortality (>15%) A RCT of Terlipressin for Type 1 HRS Sanyal et al. Gastroenterology 2008;134:1360-8. Patients Characteristics at Enrollment Age (year) No ACLF (N=1040) 58±12 ACLF (N=303) 56±11 P value .02 Male sex 655 (63.0) 195 (64.4) .66 Alcohol 483 (49.2) 170 (60.3) <.01 HCV Alcohol + HCV 210 (21.4) 38 (13.0) 95 (9.7) 27 (9.3) <.01 .83 Cause of cirrhosis mean±SD or n (%). Moreau et al. Gastroenterology 2013;144:1426-37.